Abstract

Medication monitoring is used in primary care to guide treatment and protect the patient from adverse drug events (ADEs). Early detection of ADEs may prevent their development and avoid serious or permanent effects to patient health. Published guidelines for the conduct of medication monitoring in UK primary care recommend monitoring in patients with long-term prescription of certain cardiovascular medications, including angiontensin-converting enzyme inhibitors (ACEI), loop diuretics and amiodarone. Although much evidence exists on the practice of monitoring of these medications in primary care, few studies have considered the effect of carrying out monitoring at different frequencies during long-term therapy on the risk of ADEs. Similarly, evidence of the economic effect of regular monitoring of these medications is sparse. As a consequence, policy-makers rely primarily on evidence from expert opinion as a basis for recommendations and compliance to guidelines in practice is poor. This programme of research aimed to gain an understanding of the nature of monitoring of ACEI, loop diuretics and amiodarone in primary care in England, and investigate the effectiveness and cost-effectiveness of monitoring in accordance with current guidelines.

Using electronic health records from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES), a cohort study was carried out in order to quantify the effect of monitoring the study medications at different frequencies during the course of long-term therapy. Weights based on propensity scores were used to control for confounding arising from non-random assignment into alternative monitoring regimens in retrospectively observed data. The time-to-event analysis found that conducting thyroid function tests (TFT) in amiodarone therapy below the recommended interval of once in 6 months was associated with more than a two-fold increase in the hazard rate of hypothyroidism (HR 2.79; 95% CI 1.42,5.47), thyrotoxicity (HR 2.57; 1.40,4.74) and major adverse cardiovascular events (HR 2.13; 1.31,3.45), when comparing against a group of patients monitored according to guidelines. Conversely, conducting urea & electrolyte monitoring in ACEI therapy below recommended frequency was associated with a reduced rate of hyperkalaemia treated in primary care (HR 0.57; 0.42,0.77) and hospital admission (HR 0.13;0.02,0.95). In addition, monitoring urea & electrolytes during loop diuretic therapy below recommended frequency was associated with a lower hazard rate of hypokalaemia or hyponatraemia treated in primary care (HR 0.17; 0.06,0.45). These findings support current recommendations on frequency of regular monitoring in the case of amiodarone TFT monitoring, but not in the case of ACEI or loop diuretics.

The results of the time-to-event analysis of amiodarone monitoring were used to populate a decision-analytic model designed in order to estimate the cost-effectiveness of different strategies of monitoring medication, compared to recommended practice. This analysis demonstrated that conducting TFT at recommended frequency yielded modest cost savings per patient (£129, compared to less frequent monitoring and £192 compared to more frequent monitoring option) and utility gains per patient (0.0245 quality-adjusted life-years (QALYs) compared to less frequent monitoring and 0.0543 QALYs compared to more frequent monitoring option). The probabilistic model estimated that the recommended frequency strategy had a 97% probability of being a cost saving option compared to the two alternatives. These findings support the current policy of encouraging 6-monthly monitoring of TFT in amiodarone therapy.

This programme of research has demonstrated that medication monitoring is potentially effective and cost-effective in amiodarone therapy, but did not find regular monitoring of ACEI or loop diuretic therapy to be effective. Observational research using routinely collected electronic health records can be used to gauge both the clinical and cost-effectiveness of medication monitoring in order to guide practice in this area and improve the safety of medications in primary care.